..Tetramer staining of gluten-reactive T cells in biopsy material is a useful tool for future studies of such cells in CD and could also potentially serve as a diagnostic supplement in selected cases...

..The 33-mer is thus a potent T cell stimulator that does not require further processing within APC for T cell presentation and that binds to DQ2 with a pH profile that promotes extracellular binding...

..Peptides combining the DQ2 and DQ8 signatures could be presented by DQ2, DQ8, and trans-encoded DQ heterodimers. Our findings shed light on the basis for the HLA associations in celiac disease and type 1 diabetes...

The propensity for deamidation and transamidation of peptides by transglutaminase 2 is dependent on substrate affinity and reaction conditions

..3 together with all other available DQ crystal structures and sequences led us to categorize DQA1 and DQB1 genes into two groups where any α-chain and β-chain belonging to the same group are expected to form a stable heterodimer...

Differences in the risk of celiac disease associated with HLA-DQ2.5 or HLA-DQ2.2 are related to sustained gluten antigen presentation

..2 (phenylalanine) cannot. Our findings suggest that the kinetic stability of complexes of peptide and major histocompatibility complex (MHC) is of importance for the association of HLA with disease...

A quantitative analysis of transglutaminase 2-mediated deamidation of gluten peptides: implications for the T-cell response in celiac disease

..Interestingly, TG2 is able to hydrolyze the peptide-histamine conjugates when the concentrations of substrates are lowered, thereby releasing deamidated gluten peptides that are stimulatory to T cells...

..The differential ability of DQ8 and DQ9 to harness a negatively charged anchor at P9 may result in fewer potential gluten epitopes in DQ9 patients. Our data further indicate that DQ9 is a susceptibility factor for celiac disease...

Main chain hydrogen bond interactions in the binding of proline-rich gluten peptides to the celiac disease-associated HLA-DQ2 molecule

..On the other hand, we were unable to reproduce our initial findings in the T1D case-control dataset (global p=0.6). Our results suggest that the tested FOXP3 markers do not have any major impact on susceptibility for these diseases...

Anti-PAD4 autoantibodies in rheumatoid arthritis: levels in serum over time and impact on PAD4 activity as measured with a small synthetic substrate

..2 without any other risk alleles. Epitopes commonly recognized by T cells of patients with HLA-DQ2.5 bind stably to DQ2.5 but unstably to DQ2.2. We investigated the response to gluten in patients with HLA-DQ2.2...

The molecular basis for oat intolerance in patients with celiac disease

..Most of the cells had a memory phenotype, but many other phenotypic markers showed a heterogeneous pattern. Tetramer staining of gluten-specific T cells has the potential to be used for diagnosis of celiac disease...

Helene Arentz-HansenInstitute of Immunology and Department of Medicine, Rikshopitalet, University of Oslo, Oslo, NorwayGastroenterology 123:803-9. 2002

..Only a few gliadin T-cell epitopes have been identified by earlier work. The aim of this study was to perform a systematic characterization of DQ2-restricted T-cell epitopes in alpha- and gamma-gliadins...

..Non-celiac gluten sensitivity (NCGS) is another form of gluten intolerance where the immune response is less characterized. The aim of our study was to explore and compare the early mucosal immunological events in CD and NCGS...

..Alternatively, it might be due to variable linkage disequilibria in distinct populations in the tested SNPs and a causative mutation yet to be identified or to false positive findings (type I error) in the Dutch study...

..5 peptide binding motif. This novel method, limited by library complexity and sensitivity of mass spectrometry, allows the analysis of several thousand synthetic sequences concomitantly in a simple water soluble format...

Design of new high-affinity peptide ligands for human leukocyte antigen-DQ2 using a positional scanning peptide library

..In conclusion, atorvastatin has specific effects on isolated gluten-reactive T cells and dendritic cells, but does not shut down the gluten-induced production of proinflammatory cytokines in intestinal biopsies...

..In this issue of Immunity, two papers uncover mechanisms controlling the cytolytic potential of these cells and provide evidence that lymphocyte killing of enterocytes is an important part of the celiac disease pathogenesis...

..The potential benefit of reducing the heterogeneity of clinically defined diseases by the careful phenotyping of patients, cells and lesions using advanced molecular biology and imaging techniques is highlighted...

Four novel coeliac disease regions replicated in an association study of a Swedish-Norwegian family cohort

..We examined the cytokine regulation of MHC class II molecules and the associated invariant chain (Ii) in HIMECs and investigated whether such cells can process and present a complex protein antigen to T cells...

..001), but could not find support for an association with systemic lupus erythematosus (OR=0.94; P=0.8). Altogether, we have provided further evidence of an association between autoimmune diseases and the 1858C>T polymorphism in PTPN22...

..One dimeric peptide analogue with an intermediate linker length was found to be especially effective at inhibiting DQ2 mediated antigen presentation. The implications of these findings for the treatment of celiac disease are discussed...

..Other possible treatments include cytokine therapy, and selective adhesion molecule inhibitors that interfere with inflammatory reactions, some of which are already showing promise in the clinic for other gastrointestinal diseases...

Inhibition of HLA-DQ2-mediated antigen presentation by analogues of a high affinity 33-residue peptide from alpha2-gliadin

..These results underline the primary importance of HLA-DQ alleles in susceptibility to celiac disease, and the extreme rarity of celiac patients carrying neither the DQ2 or DQ8 heterodimers nor one half of the DQ2 heterodimer alone...

..Finally, surface-exposed proline residues in the proteolytically resistant ligand were replaced with functionalized analogs, thereby providing a starting point for the design of orally active agents for blocking gluten-induced toxicity...